钾通道开放剂阿普卡林对用作旁路移植物的人体大隐静脉血管收缩的抑制作用。
Inhibition of vasoconstriction by potassium channel opener aprikalim in human conduit arteries used as bypass grafts.
作者信息
He G W, Yang C Q
机构信息
Grantham Hospital, Department of Surgery, University of Hong Kong, Hong Kong.
出版信息
Br J Clin Pharmacol. 1997 Oct;44(4):353-9. doi: 10.1046/j.1365-2125.1997.00640.x.
AIMS
Potassium channel openers (KCOs) are of potential therapeutic value. Little is known about the effect of these drugs on human conduit arteries used as coronary bypass grafts. The purpose of this study was to determine the effect of the KCO aprikalim (RP52891) on human arteries used as coronary bypass grafts with emphasis on the possible difference in the inhibitory effect on depolarizing agent-mediated rather than receptor-mediated contraction.
METHODS
Human internal mammary artery segments (IMA, n = 88) taken from 28 patients were studied. Concentration-relaxation curves for aprikalim were established in IMA precontracted with three vasoconstrictors (K+, U46619, and phenylephrine). In IMA rings incubated with aprikalim (1 or 30 microM) for 10 min concentration-contraction curves for the three vasoconstrictors were constructed.
RESULTS
Aprikalim-induced relaxation was less in K+ (37.3 +/- 6.4%) than in U46619 (80.2 +/- 7.7%, P=0.002), or phenylephrine (67.5 +/- 7.0%, P=0.038) -precontracted IMA. The EC50 for K+-(-5.40 +/- 0.12 log M) was significantly higher than that for phenylephrine (-6.43 +/- 0.30 log M, P=0.007) but not significant compared with that for U46619 (-5.81 +/- 0.11, P>0.05). Pretreatment with aprikalim depressed the contraction by phenylephrine from 140.6 +/- 27.6% to 49.3 +/- 14.1% (P=0.002) and shifted the EC50 11.0-fold higher in rings treated with 1 microM aprikalim (P=0.007). Treatment of aprikalim did not significantly reduce the K+ and U46619-induced contraction (P>0.05) but shifted the concentration-contraction curves rightward (2.8-fold higher for K+, P<0.05 and 2.2-fold higher for U46619, P<0.05).
CONCLUSIONS
This study demonstrates that aprikalim has vasorelaxant effects in human conduit arteries used as coronary artery bypass grafts contracted by a variety of vasoconstrictors and this effect is vasoconstrictor-selective with greater potency for alpha1-adrenoceptor agonists than for depolarizing agent K+. These findings provide information on the possible use of this KCO in various clinical settings.
目的
钾通道开放剂（KCOs）具有潜在的治疗价值。关于这些药物对用作冠状动脉搭桥移植物的人体 conduit 动脉的影响知之甚少。本研究的目的是确定 KCO 阿普卡林（RP52891）对用作冠状动脉搭桥移植物的人体动脉的影响，重点是对去极化剂介导而非受体介导的收缩的抑制作用可能存在的差异。
方法
研究了取自 28 名患者的人乳内动脉段（IMA，n = 88）。在与三种血管收缩剂（K⁺、U46619 和去氧肾上腺素）预收缩的 IMA 中建立阿普卡林的浓度-舒张曲线。在与阿普卡林（1 或 30 μM）孵育 十分钟的 IMA 环中构建三种血管收缩剂的浓度-收缩曲线。
结果
阿普卡林诱导的舒张在 K⁺预收缩的 IMA 中（37.3 ± 6.4%）低于在 U46619 预收缩的 IMA 中（80.2 ± 7.7%，P = 0.002）或去氧肾上腺素预收缩的 IMA 中（67.5 ± 7.0%，P = 0.038）。K⁺的 EC50（-5.40 ± 0.12 log M）显著高于去氧肾上腺素的 EC50（-6.43 ± 0.30 log M，P = 0.007），但与 U46619 的 EC50（-5.81 ± 0.11，P > 0.05）相比无显著差异。用阿普卡林预处理可使去氧肾上腺素引起的收缩从 140.6 ± 27.6%降至 49.3 ± 14.1%（P = 0.002），并使在 1 μM 阿普卡林处理的环中 EC50 升高 11.0 倍（P = 0.007）。阿普卡林处理并未显著降低 K⁺和 U46619 诱导的收缩（P > 0.05），但使浓度-收缩曲线向右移动（K⁺升高 2.8 倍，P < 0.05；U46619 升高 2.2 倍，P < 0.05）。
结论
本研究表明，阿普卡林对用作冠状动脉搭桥移植物的人体 conduit 动脉具有血管舒张作用，该动脉由多种血管收缩剂收缩，且这种作用具有血管收缩剂选择性，对α1 - 肾上腺素能激动剂的效力大于对去极化剂 K⁺的效力。这些发现为这种 KCO 在各种临床环境中的可能应用提供了信息。
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